Hokmabadi Vahideh, Khalili Azadeh, Hashemi Seyed Ali, Hedayatyanfard Keshvad, Parvari Soraya, Changizi-Ashtiyani Saeed, Bayat Gholamreza
Department of Physiology, School of Medicine, Arak University of Medical Sciences, Arak, Iran.
Department of Physiology, Pharmacology, Medical Physics, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
Iran J Basic Med Sci. 2023 Mar;26(3):343-350. doi: 10.22038/IJBMS.2023.67998.14867.
Gentamicin-induced nephrotoxicity was used as an experimental model of kidney disease. The present study was performed to assess the therapeutic role of cannabidiol (CBD) against gentamicin-induced renal damage.
Forty two male Wistar rats were randomly allocated into 6 groups (n=7), including: (1) Control, (2) Vehicle, (3) Gentamicin-treated group (100 mg/kg/day) for 10 days (GM), (4-6) 3 Gentamicin-CBD-treated groups (2.5, 5, and 10 mg/kg/day) for 10 days (GM+CBD2.5, GM+CBD5, GM+CBD10). Serum levels of BUN and Cr, renal histology as well as real-time qRT-PCR were used to investigate the pattern of changes at different levels.
Gentamicin increased serum BUN and Cr (<0.001), down-regulation of FXR (<0.001), SOD (<0.05) and up-regulation of CB1 receptor mRNA (<0.01). Compared to the control group, CBD at 5 decreased (<0.05) and at 10 mg/kg/day increased the expression of FXR (<0.05). Nrf2 expression in CBD groups was increased (<0.001 vs. GM). The expression of TNF-α compared to the control and GM groups, was significantly increased in CBD2.5 (<0.01) and CBD10 (<0.05). Compared to the control, CBD at 2.5 (<0.01), 5 (<0.001) and 10 (<0.001) mg/kg/day significantly increased the expression of CB1R. Up-regulation of CB1R in the GM+CBD5, was significantly higher (<0.05) than the GM group. Compared to the control group, the most significant increase in CB2 receptor expression was observed at CBD10 (<0.05).
CBD particularly at 10 mg/kg/day might be of significant therapeutic benefit against such renal complications. Activating the FXR/Nrf2 pathway and counteracting the deleterious effects of CB1 receptors via CB2 receptors scale-up could be part of the protective mechanisms of CBD.
庆大霉素诱导的肾毒性被用作肾脏疾病的实验模型。本研究旨在评估大麻二酚（CBD）对庆大霉素诱导的肾损伤的治疗作用。
42只雄性Wistar大鼠随机分为6组（n = 7），包括：（1）对照组，（2）赋形剂组，（3）庆大霉素治疗组（100 mg/kg/天），持续10天（GM），（4 - 6）3个庆大霉素 - CBD治疗组（2.5、5和10 mg/kg/天），持续10天（GM + CBD2.5、GM + CBD5、GM + CBD10）。采用血清尿素氮（BUN）和肌酐（Cr）水平、肾脏组织学以及实时定量逆转录 - 聚合酶链反应（qRT - PCR）来研究不同水平的变化模式。
庆大霉素使血清BUN和Cr升高（<0.001），法尼醇X受体（FXR）、超氧化物歧化酶（SOD）下调（<0.001、<0.05），大麻素受体1（CB1）受体mRNA上调（<0.01）。与对照组相比，5 mg/kg/天的CBD使FXR表达降低（<0.05），而10 mg/kg/天的CBD使FXR表达增加（<0.05）。CBD组中核因子E2相关因子2（Nrf2）表达增加（与GM组相比，<0.001）。与对照组和GM组相比，CBD2.5组肿瘤坏死因子 - α（TNF - α）表达显著增加（<0.01），CBD10组TNF - α表达显著增加（<0.05）。与对照组相比，2.5（<0.01）、5（<0.001）和10（<0.001）mg/kg/天的CBD显著增加CB1R的表达。GM + CBD5组中CB1R的上调显著高于GM组（<0.05）。与对照组相比，CBD10组中CB2受体表达增加最为显著（<0.05）。
CBD尤其是10 mg/kg/天可能对这类肾脏并发症具有显著的治疗益处。激活FXR/Nrf2通路以及通过上调CB2受体抵消CB1受体的有害作用可能是CBD的保护机制的一部分。
